CHARACTERIZATION OF THE VON-WILLEBRAND-FACTOR GENE (VWF) IN VON-WILLEBRAND DISEASE TYPE-III PATIENTS FROM 24 FAMILIES OF SWEDISH AND FINNISH ORIGIN

Twenty-four patients with von Willebrand disease type m were screened for mutations in the von Willebrand factor (VWF) gene using the PCR te chnique, followed by direct sequencing. More than 250 kb of genomic DN A were sequenced, including the promoter and coding regions (52 exons) of the VWF gene from 24 patients. In addition to the previously repor ted mutations of a single cytosine deletion in exon 18 and the nonsens e mutations in exons 28, 32, and 45, nine new mutations were detected: two nonsense mutations in exons 15 and 16, one allele with a thymidin e insertion in exon 14, one allele with a cytosine insertion in exon 2 8, one 20-bp deletion in exon 15, one mutation in the donor splice sit e of exon 43, and three missense mutations in exons 28, 49, and 51. Fo rty-two mutant chromesomes were identified (42/48); 11 probands are ho mozygous for the mutations, and 8 are compound heterozygous. In additi on, a new subfamily of the ALu sequence in the promoter region and 10 new polymorphisms were identified. (C) 1994 Academic Press, Inc.